Protective Effect of Ginsenoside Rg5 on Hypoxia/Reoxygenation- Induced H9c2 Cardiomyocytes by Correcting Free Fatty Acids β- oxidation

Clinically, the in-hospital mortality rate of cardiogenic shock (CS) is approximately 50%. In CS, metabolic pathways in the body undergo “embryonal transformation,” in which metabolic processes transform free fatty acids (FFAs) to glucose. Shenfu injection (SFI) treatment has exhibited a positive effect on cardiogenic shock, and ginsenoside Rg5 (G-Rg5) is the anticardiogenic shock component of SFI. In this study, we aimed to investigate the myocardial protective effect and mechanism of G-Rg5 in myocardial energy metabolism, especially from the perspective of FFA β-oxidation, one of the most crucial lipid metabolism pathways. Cardiomyocytes were exposed to hypoxia-reoxygenation (H/R) and treated with G-Rg5. MTT analysis was used to determine the viability of H9c2 cardiomyocytes under different interventions with G-Rg5. The levels of lactate dehydrogenase (LDH) and FFA were detected using ELISA, and adenosine triphosphate (ATP) was determined using high-performance liquid chromatography (HPLC). Furthermore, the expression of NR4A1 was determined by RT-qPCR, and the levels of AMPKα, p-AMPKα, and GPX4 were detected by western blotting to explore the underlying mechanism. We observed that G-Rg5-protected H9c2 cardiomyocytes exhibited better FFA β-oxidation regulation, thereby producing an increased abundance of ATP. G-Rg5 may correct FFA β-oxidation by regulating the levels of NR4A1, AMPKα, p-AMPKα, and GPX4. Therefore, G-Rg5 is a promising drug for CS treatment.